Mean Arterial Pressure After Out-of-hospital Cardiac Arrest

NCT05486884 | Recruiting DMC

• 1 other identifier: CHM-2022/S03/07
• Study Type: interventional
• Target: 1,380
• Locations: 1 country
• Sites: 27

Brief Summary

Out-of-hospital cardiac arrest is a public health problem for which overall survival is below 10%. Post-cardiac arrest syndrome is the principal cause of death in intensive care units (ICU), due to refractory shock or brain injuries secondary to anoxia. Brain anoxia is responsible for severe neurological sequelae that may be aggravated by cerebral hypoperfusion during the first few hours after the return of spontaneous circulation. Current recommendations are to ensure that arterial blood pressure is sufficient for the perfusion of organs, but no minimum threshold mean arterial pressure (MAP) has been defined. In practice, most teams target a MAP of at least 65 mmHg. Several observational studies have shown a correlation between MAP and neurological prognosis, patients with a higher initial MAP having a better outcome. Recent pilot studies have demonstrated the feasibility of increasing the target MAP after cardiac arrest, but conflicting results have been obtained concerning patient prognosis. These findings may be explained by changes to the autoregulation of the brain after cardiac arrest, with a shift of the curve towards the right, or its abolition. Cerebral blood flow is dependent on MAP, and a target MAP of 65 mmHg for these patients may result in insufficient brain perfusion. Conversely, a too high MAP might cause brain lesions due to vasogenic edema, hemorrhagic complications or excess perfusion in conditions of diminished brain metabolism. An interventional study is required to evaluate the effect of increasing MAP on neurofunctional outcome after cardiac arrest. Given the data available for brain autoregulation, the correlation between MAP and prognosis, and the risks theoretically associated with a higher MAP, investigator plans to compare a standard threshold of MAP (≥ 65 mmHg) with a high threshold of MAP (≥ 90 mmHg). Investigator hypothesizes that a high MAP within the first 24 hours after cardiac arrest will improve neurofunctional outcome.

Conditions

Cardiac Arrest; Out-of-hospital Cardiac Arrest (OHCA)

Keywords

cardiac arrest; outcome; cerebral blood flow; mean arterial pressure

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with a good neurofunctional outcome 180 days after inclusion

  Good neurofunctional outcome will be defined by a modified Rankin scale (mRS) of 0 to 3.This score is a global evaluation scale for disability, with seven levels (0 = no symptoms; 6 = patient dead).This score will be measured by psychologist who will be blinded to the randomization arm.

  180 days after inclusion

Secondary Outcomes (7)

• Proportion of patients alive at Intensive Care Unit discharge, at hospital discharge, at day 28 (D28) and six months (D180) after inclusion

  From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks), from hospital admission to hospital discharge (up to 12 weeks), 28 days and 180 days after inclusion

• Proportion of patients alive at Intensive Care Unit discharge with good neurofunctionnal outcome

  From Intensive Care Unit admission to Intensive Care Unit discharge (up to 3 weeks)

• Quality of life six months after inclusion

  6 months after inclusion

• Evaluation of Clinical Frailty at six months after inclusion

  Six months after inclusion

• Number of ICU-free days at Day 28

  Day 28

Other Outcomes (9)

• Cardiovascular complications

  within 7 days after inclusion

• Neurological complications

  within 7 days of inclusion

• Cutaneous complications within 7 days of inclusion

  within 7 days of inclusion

Study Arms (2)

high MAP threshold

EXPERIMENTAL

Norepinephrine will be titrated to maintain MAP ≥ 90 mmHg. This threshold will be maintained for the 24 hours following inclusion by the perfusion of norepinephrine at an appropriate dose. From 24 hours after inclusion until ICU discharge, a MAP ≥ 65 mmHg will be targeted

Procedure: Maintain MAP ≥ 90 mmHg

standard MAP threshold

ACTIVE COMPARATOR

Norepinephrine will be titrated to maintain MAP ≥ 65 mmHg. This target MAP will be maintained for 24 hours after randomization through the perfusion of norepinephrine at an appropriate flow rate. From 24 hours after inclusion until ICU discharge, a MAP ≥ 65 mmHg will be targeted

Procedure: Maintain MAP ≥ 65 mmHg

Interventions

Maintain MAP ≥ 90 mmHg PROCEDURE

Maintain MAP ≥ 90 mmHg for the 24 hours following inclusion by perfusion of norepinephrine

high MAP threshold

Maintain MAP ≥ 65 mmHg PROCEDURE

Maintain MAP ≥ 65 mmHg for 24 hours after randomization through the perfusion of norepinephrine

standard MAP threshold

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admission to ICU following an out-of-hospital cardiac arrest with an initially shockable or non-shockable rhythm ;
• Sustained ROSC defined as 20 minutes with signs of circulation without the need for chest compressions;
• Under invasive mechanical ventilation for coma, defined as a Glasgow score ≤ 8/15;

You may not qualify if:

• Age \< 18 years ;
• In-hospital cardiac arrest (first cardiac arrest);
• Unwitnessed CA with initial rhythm of asystole
• Delay between ROSC and attempting randomisation \> 6 hours ;
• Cardiac arrest in a context of multiple trauma ;
• Cardiac arrest in a context of hemorrhagic shock or severe hemorrhage necessitating hemostasis (surgery or radiological or endoscopic hemostasis) ;
• Cardiac arrest secondary to an acute brain disease (ischemic or hemorrhagic stroke, subarachnoid hemorrhage, severe traumatic brain injury) ;
• Refractory shock :
• Defined as a MAP \< 65 mmHg for more than one hour on norepinephrine or epinephrine at a dose \> 1 µg/kg/min despite adequate fluid resuscitation ;
• Known allergy to norepinephrine or to any of its excipients;
• Modified Rankin score of 4 or 5 before cardiac arrest ;
• Pregnancy or breast feeding ;
• Adult patient deprived of freedom or under legal protection (patients under guardianship or curatorship) (article L1121-6 of the French Health Code) ;
• Non-French speaking;
• Patient already included in this trial ;

Sponsors & Collaborators

• Centre Hospitalier le Mans: lead

Study Sites (27)

CHU Brest - Hôpital de La Cavale Blanche

Brest, 29609, France

RECRUITING

CH Brive

Brive-la-Gaillarde, 19100, France

RECRUITING

CHU Caen

Caen, 14000, France

RECRUITING

CH Cholet

Cholet, 49300, France

RECRUITING

CH Dieppe

Dieppe, 76200, France

RECRUITING

CHU Dijon - Hôpital F. Mitterrand

Dijon, 21079, France

RECRUITING

CHD Vendée

La Roche-sur-Yon, 85925, France

RECRUITING

CH Versailles

Le Chesnay, 78150, France

NOT YET RECRUITING

Centre Hospitalier Du Mans

Le Mans, 72000, France

RECRUITING

CH Dr Schaffner

Lens, 62300, France

RECRUITING

CHU Lille

Lille, 59037, France

RECRUITING

CHU Limoges

Limoges, 87042, France

RECRUITING

APHM - Hôpital de la Timone

Marseille, 13005, France

RECRUITING

Hôpital Jacques Cartier

Massy, 91300, France

NOT YET RECRUITING

CHU Nantes

Nantes, 44093, France

NOT YET RECRUITING

CHU Nice - Hôpital Pasteur

Nice, 06001, France

RECRUITING

CHU Nice - Hôpital Archet

Nice, 06202, France

RECRUITING

CHU Nîmes

Nîmes, 30029, France

RECRUITING

CHR Orléans

Orléans, 45067, France

NOT YET RECRUITING

Hôpital Cochin

Paris, 75014, France

NOT YET RECRUITING

APHP - Hôpital Européen Georges Pompidou (HEGP)

Paris, 75015, France

RECRUITING

CHU Poitiers

Poitiers, 86021, France

RECRUITING

CHU Rennes

Rennes, 35000, France

RECRUITING

Centre Cardiologique du Nord

Saint-Denis, 93207, France

RECRUITING

CHRU Strasbourg - Nouvel Hôpital Civil

Strasbourg, 67091, France

RECRUITING

CHRU Tours - Hôpital Bretonneau

Tours, 37044, France

RECRUITING

CH Bretagne Atlantique

Vannes, 56000, France

RECRUITING

Related Publications (1)

• Chudeau N, Saulnier P, Parot-Schinkel E, Lascarrou JB, Colin G, Barbar SD, Painvin B, Pichon N, Du Cheyron D, Marchalot A, Jarousseau F, Delbove A, Morichau-Beauchant T, Girardie P, Salmon Gandonniere C, Thille AW, Quenot JP, Bailly P, Goudelin M, Martino F, Nigeon O, Merdji H, Brechot N, Bourenne J, Bougouin W, Muller G, Jozwiak M, Doyen D, Rouanet E, Cariou A, Guitton C; AfterROSC Network; CRICS TRIGGERSep F-CRIN Network. Mean arterial pressure after out-of-hospital cardiac arrest (METAPHORE): study protocol for a multicentre controlled trial with blinded primary outcome assessor. BMJ Open. 2025 Apr 25;15(4):e096997. doi: 10.1136/bmjopen-2024-096997.

  PMID: 40280607 DERIVED

MeSH Terms

Conditions

Heart Arrest; Out-of-Hospital Cardiac Arrest

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Christelle JADEAU

CONTACT

+33244710781; cjadeau@ch-lemans.fr

Nicolas CHUDEAU

CONTACT

+33243432458; nchudeau@ch-lemans.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Score mRS will be measured by a psychologist during a telephone interview 180 days after inclusion. The psychologist will be blinded to the randomization arm
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, multicenter, randomized, controlled, open study

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: August 4, 2022
• Study Start: September 28, 2024
• Primary Completion (Estimated): March 28, 2028
• Study Completion (Estimated): March 28, 2028
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

FR (27)